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The one-pot triflation/radical trifluoromethylation/triflation of imines leading to CF3-substituted vinyl trifluoromethanesulfonamides is described. The reaction proceeds via the radical trifluoromethylation of vinyl trifluoromethanesulfonamides as the key step. This reaction is suitable for a variety of imines that contain halogen atoms, electron-donating groups, or electron-withdrawing groups, leading to moderate to good yields. Vinyl trifluoromethanesulfonamides can act as bifunctional reagents whereby they serve as both the trifluoromethyl radical source and the radical acceptor.

We developed a new transition-metal-free intermolecular Claisen rearrangement process to introduce allyl and allenyl groups into the α position of tertiary amides. In this transformation, amides were activated by trifluoromethanesulfonic anhydride to produce the keteniminium ion intermediates that exhibit strong electrophilic activity. This atom-economical process delivers α position-modified amides under mild conditions in moderate to good yields and showcases a broad substrate compatibility.

N-Boc-5-formylpyrazol-4-amines reacted with 1,3-cyclohexanediones in AcOH–1,4-dioxane medium in the presence of pyrrolidine, resulting in the formation of pyrazolo[4,3-b]quinolin-8-one derivatives that were converted into the respective oximes. A reaction of the latter with trifluoromethanesulfonic anhydride under mild conditions was used to synthesize hexahydropyrazolo[3',4':5,6]pyrido[3,2-b]-azepin-4-ium trifluoromethanesulfonates.

2-Iodosylbenzoic acid in the presence of trifluoromethanesulfonic anhydride is an efficient oxidant and electrophilic reagent useful for preparation of the corresponding alkenyl and aryliodonium salts. Compared to the previously reported methods of electrophilic activation of 2-iodosylbenzoic acid, this procedure is compatible with acid-sensitive functional groups, requires mild reaction conditions, and affords products in higher yields.

An examination of the efficacy of combining physisorbed and chemisorbed passivation strategies on crystalline Si has been performed. This report compares the influence of a linear alkyl adsorbate tethered by either a Si-C or Si-Si linkage, prepared by reaction of Si(111) with organometallic Grignard reagents or organosilanes, respectively. These modified surfaces are first analyzed and compared by IR and X-ray photoelectron spectroscopies. Their behavior toward a known potent physisorbate, trifluoromethanesulfonic anhydride (Tf2O), is then examined. Microwave photoconductivity measurements were obtained which indicate that, while Tf2O shows a beneficial lowering of surface recombination on both surface types initially, only surfaces featuring Si-C linkages exhibit long-lasting suppressed surface recombination. The data for Grignard-treated Si after exposure to Tf2O in fact represent the longest known report of surface recombination suppression by a physisorbate. Conversely, the data for the Si surfaces prepared by dehydrogenative coupling suggest that these passivating groups themselves introduce defect states that cannot be ameliorated by Tf2O physisorption.

A new and convenient protocol has been proposed for the transformation of aldoximes to nitriles using trifluoromethanesulfonic anhydride and triethylamine. The proposed method allows a range of aldoximes, including aromatic, heterocyclic, aliphatic, and cycloaliphatic aldoximes, to be converted to the corresponding nitriles in good to excellent yields.

An ongoing challenge in trifluoromethylthiolation reactions is the use of less expensive and easily available trifluoromethylthio sources. Herein, we disclose an unprecedented usage of trifluoromethanesulfonic anhydride (Tf2 O) as a radical trifluoromethylthiolating reagent. Hydrotrifluoromethylthiolation of unactivated alkenes and alkynes with Tf2 O in the presence of PMePh2 and H2 O under visible-light photoredox catalysis gave the addition products. The trifluoromethylthio radical (. SCF3 ) was first formed from Tf2 O through a photoredox radical processes and deoxygenative reduction of PMePh2 , and H2 O serves as the H-atom donor for the hydrotrifluoromethylthiolation reaction. This reaction provides a new strategy for radical trifluoromethylthiolation.

Ammonium pertechnetate reacts in mixtures of trifluoromethanesulfonic anhydride and trifluoromethanesulfonic acid under final formation of ammonium pentakis(trifluoromethanesulfonato)oxidotechnetate(V), (NH$_{4}$)$_{2}$ [TcO(OTf) $_{5}$]. The reaction proceeds only at exact concentrations and under the exclusion of air and moisture via pertechnetyl trifluoromethanesulfonate, [TcO$_{3}$(OTf)], and intermediate Tc$^{VI}$ species. $^{99}$Tc nuclear magnetic resonance (NMR) has been used to study the Tc$^{VII}$ compound and electron paramagnetic resonance (EPR), $^{99}$Tc NMR and X-ray absorption near-edge structure (XANES) experiments indicate the presence of the reduced technetium species. In moist air, (NH$_{4}$)2[TcO(OTf)5] slowly hydrolyses under formation of the tetrameric oxidotechnetate(V) (NH$_{4}$)$_{4}$ [{TcO(TcO$_{4}$)$_{4}$}$_{4}$] ���10 H$_{2}$O. Single-crystal X-ray crystallography was used to determine the solid-state structures. Additionally, UV/Vis absorption and IR spectra as well as quantum chemical calculations confirm the identity of the species.

In this paper, we report the regioselective synthesis of 3,5‐disubstituted isoxazoles by 1,3‐dipolar cycloaddition between alkynyl dipolarophiles and nitrile oxide dipoles generated in‐situ from O‐silylated hydroxamic acids in the presence of trifluoromethanesulfonic anhydride and NEt3. Thanks to the mild, metal‐free and oxidant‐free conditions that this strategy offers, the reaction was successfully applied to a wide variety of alkynyl dipolarophiles, demonstrating the tolerance of this approach to diverse functional groups. In particular, we have shown that the method was compatible with biological molecules such as peptides and peptide nucleic acids (PNA). This protocol constitutes another example of metal‐free 1,3‐dipolar cycloaddition leading to the regioselective formation of isoxazoles.

A mild and efficient procedure has been developed for the synthesis of 3-amino-1-benzofurans by intramolecular cyclization of the corresponding N,N-disubstituted phenoxyacetamides under the action of trifluoromethanesulfonic anhydride in the presence of 2-fluoropyridine in methylene chloride at room temperature. The proposed novel and efficient protocol has been successfully utilized to obtain a wide series of 3-amino-1-benzofurans with various substituents in the benzene ring and amino group.

An efficient and mild protocol for the direct and flexible synthesis of 3-amino-1,4-diynes bearing an aza-quaternary carbon from tertiary amides and lactams has been established. The one-pot method consists of in situ activation of amides with trifluoromethanesulfonic anhydride, followed by double addition of alkynyllithium reagents at a concentration of 0.5 mol·L-1 in dichloromethane. This constitutes an extension of the method of direct reductive bisalkylation of amides that allows both employing alkynyllithium reagents as the first-addition nucleophiles and incorporating an alkynyl group as the first-introduced group.

The synthesis of 6-aminoisomannide is easily achieved starting from the renewable, inexpensive, and commercially available isosorbide in 66% overall yield. A biocatalyzed highly regioselective acetylation of the 3-endo hydroxyl group of isosorbide was followed by the stereospecific interconversion of the 6-exo hydroxyl group into an azido group, through reaction with trifluoromethanesulfonic anhydride, followed by nucleophilic displacement of the triflate group by sodium azide. Finally, reduction of the azido group and deacetylation of the 3-hydroxy group were performed in one pot using LiAlH4.

The first copper and zinc copromoted trifluoromethylation using trifluoromethanesulfonic anhydride (Tf2O) as a trifluoromethylating reagent has been developed. The reaction of alkenes or alkynes with Tf2O in the presence of CuX2 (X = Br, Cl), Zn powder, and 2,2'-bipyridine affords bromo(chloro)trifluoromethylated products in good yields. CuX2 plays a dual role as the catalyst and halide source, whereas 2,2'-bipyridine acts as both the activation reagent and ligand.

Herein, we conceptualized a transient mediator approach that has the capability of para-selective C–H functionalization of monosubstituted aromatics. This approach is enabled by in situ generation of a versatile sulfonium salt via highly electrophilic phenoxathiine or thianthrene dication intermediate which can be readily generated from its sulfoxide with trifluoromethanesulfonic anhydride. Preliminary mechanistic study implied that the remarkable para selectivity might be related to the incredible electrophilicity of thianthrene dication intermediate. The versatility of this approach was demonstrated via para-borylation of various monosubstituted simple aromatics combining the sulfonium salt formation with further photocatalyzed transformation.

A large number of reagents have been developed for the synthesis of trifluoromethylated compounds. However, an ongoing challenge in trifluoromethylation reaction is the use of less expensive and practical trifluoromethyl sources. We report herein the unprecedented direct trifluoromethylation of (hetero)arenes using trifluoromethanesulfonic anhydride as a radical trifluoromethylation reagent by merging photoredox catalysis and pyridine activation. Furthermore, introduction of both the CF3 and OTf groups of the trifluoromethanesulfonic anhydride into internal alkynes to access tetrasubstituted trifluoromethylated alkenes was achieved. Since trifluoromethanesulfonic anhydride is a low-cost and abundant chemical, this method provides a cost-efficient and practical route to trifluoromethylated compounds.

A new strategy to construct allylamines through reductive alkenylation of secondary amides with enamines is reported. The method features the use of trifluoromethanesulfonic anhydride as an activation reagent of amides, and enamines as unconventional alkenylation reagents. In this manner, enamines serve as surrogates of alkene carbanions instead of the classical enolates equivalents. A possible mechanism involving a Hoffmann-like elimination of the amine-borane complex intermediate is proposed.

An intermolecular biaryl coupling reaction of phenol derivatives activated by a sulfonium salt formed from diphenyl sulfoxide and trifluoromethanesulfonic anhydride has been developed. The method is a rapid, one-pot reaction leaving no trace of the sulfonium moiety in the coupling products. Tri-substituted phenyl ethers also gave coupling products in moderate yields.

A concise synthesis of (S)-3-hydroxytetrahydropyran from natural l -glutamic acid has been developed. The intramolecular etherification starting from 1,5-diol was promoted by trifluoromethanesulfonic anhydride. The clinnamates of the alcohols were prepared for accurately determining the optical purity by HPLC method.

Diversely substituted arylsilyl triflates, as aryne precursors for aryne cycloaddition reactions, were accessed from benzodioxasilines. Catalytic reductive C H ortho- silylation of phenols with traceless acetal directing groups was exploited to prepare benzodioxasilines. Sequential addition of MeLi and then trifluoromethanesulfonic anhydride to benzodioxasilines provided arylsilyl triflates in a single pot. Notably, this approach was successfully utilized to prepare sterically hindered 1,2,3-trisubstituted arylsilyl triflates, which ultimately underwent fluoride-mediated aryne cycloaddition.

N-Allyl- and N-propargyltrifluoromethanesulfonimides were synthesized by reaction of trifluoromethanesulfonic anhydride with allylamine and propargylamine. Some reactions of the resulting unsaturated derivatives were studied, in particular bromination, dehydrobromination of the bromination product, and nucleophilic substitution of bromine.

Cyclic phosphonium anhydrides generated from bis-phosphine oxides and trifluoromethanesulfonic anhydride are shown as general coupling reagents in a dehydrative glycosylation reaction of C1-hemiacetals. This reaction protocol is characterized by a broad substrate scope and high yields, including reactions of O-, C-, N-, and S-based nucleophiles with furanose, pyranose, and deoxysugar donors.

The formal synthesis of (+)-kopsihainanine A has been achieved via stereoselective reduction of tetracyclic iminium ion intermediates (24). However, attempts to synthesize (+)-limaspermidine by reduction of the same tetracyclic iminium ion intermediates have failed. The synthesis features a Suzuki cross-coupling reaction, a cyclization reaction mediated by trifluoromethanesulfonic anhydride, and stereoselective reduction of an iminium ion.

Ce mémoire est séparé en deux parties distinctes visant à analyser les travaux récents relatifs à l’utilisation de deux molécules très réactives en synthèse organique : l’anhydride triflique (Tf2O) et le trifluorométhyldiazométhane. Dans un premier temps, la chimie d’activation des amides par l’anhydride triflique a été appliquée à la synthèse d’amidines libres secondaires et tertiaires. Ces molécules trouvent des applications tant dans la synthèse de produits naturels qu’en chimie médicinale. Bien que leur purification à petite échelle soit relativement complexe, leur synthèse et leur caractérisation ont été réalisées avec succès. Ensuite, les travaux ont été orientés vers la trifluorométhylation de molécules organiques en vue de transformer les intermédiaires activés (obtenus suite à l’activation des amides) en trifluorométhylcétones. Cependant, cette voie de synthèse s’est avérée inefficace. Un autre réactif de trifluorométhylation a alors été exploité : le trifluorométhyldiazométhane. La seconde partie de cet ouvrage, détaille la synthèse efficace et sécuritaire du trifluorométhyldiazométhane en débit continu. Le trifluorométhyldiazométhane a par la suite été utilisé dans la synthèse de pyrazolines trifluorométhylées. Une tendance réactionnelle influençant la tautomérie spontanée ou non de ces molécules en fonction de la nature du substrat a été observée. Les pyrazolines trifluorométhylées sont d’un intérêt certain pour le domaine pharmaceutique, et servent également comme précurseurs de cyclopropanes trifluorométhylés. Finalement, quelques idées et projets futurs seront proposés, notamment en ce qui concerne la synthèse en débit continu de cyclopropanes trifluorométhylés, de manière efficace et potentiellement énantiosélective., This work is separated in two distinct parts aiming to describe the recent advances concerning the use of highly reactive molecules such as trifluoromethanesulfonic anhydride (Tf2O) and trifluormethyldiazomethane in organic synthesis. In the first section, the amide activation strategy using triflic anhydride was applied in order to synthesize free secondary and tertiary amidines. Those molecules find numerous applications, particularly in natural product synthesis and medicinal chemistry. Although their purification on small scale is quite difficult, their synthesis and caracterization were successfully achieved. Next, investigations were conducted towards the trifluoromethylation of organic compounds. The idea was to trifluoromethylate highly electronegative activated amides in order to transform them into trifluoromethylketones. Unfortunately, this route appeared to be uneffective and was switched to another promising trifluoromethylating source : Trifluormethyldiazomethane. In the second section, the safe and efficient synthesis of trifluoromethyldiazomethane in continuous flow is described. That diazo compound was then used in the synthesis of trifluoromethylated pyrazolines. A reactivity trend was unveiled as those molecules spontaniously tautomerize (or not) depending on the nature of the substrate. Trifluoromethylated pyrazolines are interesting compounds on their own, especially for the pharmaceutical industry, but also serve as precursors to trifluoromethylated cyclopropanes. Finaly, some ideas and related future projects are discribed, in particular in what should be an efficient and possibly enantioselective synthesis of trifluoromethylated cyclopropanes in continuous flow.

Novel, non-racemic 4,5-unsubstituted N-carbamoyl-2,3-dihydroisoxazoles are prepared in moderate to good yields from the corresponding 5-hydroxyisoxazolidines under mild reaction conditions using the Tf2O/2-chloropyridine couple in N-methyl-2-pyrrolidone.

We report the first one-pot reductive homocoupling reaction of secondary amides and cross-coupling reaction of secondary amides with ketones to give secondary vicinal diamines and amino alcohols. This method relies on the direct generation of α-amino carbon radicals from secondary amides by activation with trifluoromethanesulfonic anhydride, partial reduction with triethylsilane and samarium diiodide-mediated single-electron transfer. The reactions were run under mild conditions and tolerated several functional groups.

(+)-Pisiferic acid (1) was converted into (+)-12-O-methoxymethylpisiferol (5c) in 3 steps. The rearrangement of 5c with trifluoromethanesulfonic anhydride in pyridine provided (−)-12-O-methoxymethylpisiferin (6c), which was converted into icetexane phenols 6a, 11, and 14. The ortho-selective oxygenation of 6a and 14 with stabilized 2-iodoxybenzoic acid (SIBX), followed by the reduction of intermediary quinones afforded (−)-barbatusol (2) and (+)-rosmaridiphenol (4) in 49% and 35%, respectively. The oxygenation of 11 using potassium 5-methyl-2-iodobenzenesulfonate (pre-MIBS) with Oxone® followed by reduction gave (+)-demethylsalvicanol (3) in 59% yield.

A regioselective synthesis of pyridines by the addition of malonate anions to pyridine N-oxide derivatives, which have been activated by trifluoromethanesulfonic anhydride, is reported. The reaction selectively affords either 2- or 4-substituted pyridines in good yields.

The reaction of urea derivatives that contain the phenothiazine unit with trifluoromethanesulfonic anhydride in the presence of electron-rich aromatic compounds leads to the formation of arenecarboxamides. The reaction has been successfully demonstrated for several inter- and intramolecular systems.

2,2-Bis(alkoxy-NNO-azoxy)propane-1,3-diols react with sulfonyl chlorides and trifluoromethanesulfonic anhydride in the presence of bases affording previously unknown methane-, trifluoromethane-, benzene and toluenesulfonates (sulfonic esters) of 2-bis(methoxy- and ethoxy-NNO-azoxy)propane-1,3-diols. The triflates are thermally less stable than mesylates, benzenesulfonates, and tosylates of the corresponding diols.

An effective, novel and rapid one-pot three-component route to quinazolin-4(3H)-ones from commercially available starting materials is described. Isatoic anhydride reacts with acyl chlorides and different amines using a combination of trifluoromethanesulfonic anhydride (Tf2O) and 2-chloropyridine (2-ClPy) to produce the corresponding quinazolinone derivatives in good to excellent yields.

Carbon–carbon bond formation by metal-free cross-coupling of two reactants with low reactivity represents a challenge in organic synthesis. Secondary amides and alkenes are two classes of bench-stable compounds. The low electrophilicity of the former and low nucleophilicity of the latter make the direct coupling of these two partners challenging yet highly desirable. We report herein an unprecedented intermolecular reaction of secondary amides with alkenes to afford α,β-unsaturated ketimines or enones, which are versatile intermediates for organic synthesis and are prevalent in bioactive compounds and functional materials. Our strategy relies on the chemoselective activation of the secondary amide with trifluoromethanesulfonic anhydride (Tf2O)/2-fluoropyridine to generate a highly reactive nitrilium intermediate, which reacts efficiently with alkenes. This metal-free synthesis is characterized by its mild reaction conditions, excellent functional group tolerance and chemoselectivity, allowing the preparation of multi-functionalized compounds without using protecting groups.